A major objective of our present research program is to try to clarify the various reactions that occur in the early events of the intrinsic and extrinsic pathways of blood coagulation. Thus, we have spent considerable effort on the isolation and characterization of those proteins participating in the early phase of coagulation so that we can carefully study the interaction of these proteins in purified systems. Accordingly, prekallkrein, factor XII, high molecular weight kininogen, and factor XI have been isolated and characterized from bovine plasma. We are also continuing our investigations on factor VIII in order to clarify the role of this protein in the coagultion pathway. At the present time, most of our effort is focused on the purification and stabilization of this trace plasma protein. Our efforts during the coming year will also include studies on the effects of activated Protein C on the coagulation process. This protein readily inactivates factor V by minor proteolysis. A detailed study of the mechanism of inactivation of factor V by activated Protein C is now under investigation.